Inferring structural variant cancer cell fraction

• DOI: 10.1038/s41467-020-14351-8
• Publication Date: 2020-02-05T19:03:29Z
• Authors: Marek Cmero; Ke Yuan; Cheng Soon Ong; Jan Schröder; ; David J. Adams; Pavana Anur; Rameen Beroukhim; Paul C. Boutros; David D. L. Bowtell; Peter J. Campbell; Shaolong Cao; Elizabeth L. Chri...; Yupeng Cun; Kevin J. Dawson; Jonas Demeulemeester; Stefan C. Dentro; Amit G. Deshwar; Nilgun Donmez; Ruben M. Drews; Roland Eils; Yu Fan; Matthew W. Fittall; Dale W. Garsed; Moritz Gerstung; Gad Getz; Santiago Gonzalez; Gavin Ha; Kerstin Haase; Marcin Imielinski; Lara Jerman; Yuan Ji; Clemency Jolly; Kortine Kleinheinz; Juhee Lee; Henry Lee-Six; Ignaty Leshchiner; Dimitri Livitz; Salem Malikic; Iñigo Martincorena; Thomas J. Mitchell; Quaid D. Morris; Ville Mustonen; Layla Oesper; Martin Peifer; Myron Peto; Benjamin J. Raphael; Daniel Rosebrock; Yulia Rubanova; S. Cenk Sahinalp; Adriana Salcedo; Matthias Schlesner; Steven E. Schumacher; Subhajit Sengupta; Ruian Shi; Seung Jun Shin; Paul T. Spellman; Oliver Spiro; Lincoln D. Stein; Maxime Tarabichi; Peter Van Loo; Shankar Vembu; Ignacio Vázquez-G...; Wenyi Wang; David C. Wedge; David A. Wheeler; Jeffrey A. Winter...; Tsun-Po Yang; Xiaotong Yao; Kaixian Yu; Hongtu Zhu; Niall M. Corcoran; Tony Papenfuss; Christopher M. Ho...; Florian Markowetz; Geoff Macintyre; ; Lauri A. Aaltonen; Federico Abascal; Adam Abeshouse; Hiroyuki Aburatani; David J. Adams; Nishant Agrawal; Keun Soo Ahn; Sung-Min Ahn; Hiroshi Aikata; Rehan Akbani; Kadir C. Akdemir; Hikmat Al-Ahmadie; Sultan T. Al-Sedairy; Fatima Al-Shahrour; Malik Alawi; Monique Albert; Kenneth Aldape; Ludmil B. Alexandrov; Adrian Ally; Kathryn Alsop; Eva G. Alvarez; Fernanda Amary; Samirkumar B. Amin; Brice Aminou; Ole Ammerpohl; Matthew J. Anderson; Yeng Ang; Davide Antonello; Pavana Anur; Samuel Aparicio; Elizabeth L. Appe...; Yasuhito Arai; Axel Aretz; Koji Arihiro; Shun-ichi Ariizumi; Joshua Armenia; Laurent Arnould; Sylvia Asa; Yassen Assenov; Gurnit Atwal; Sietse Aukema; J. Todd Auman; Miriam R. R. Aure; Philip Awadalla; Marta Aymerich; Gary D. Bader; Adrian Baez-Ortega; Matthew H. Bailey; Peter J. Bailey; Miruna Balasundaram; Saianand Balu; Pratiti Bandopadh...; Rosamonde E. Banks; Stefano Barbi; Andrew P. Barbour; Jonathan Barenboim; Jill Barnholtz-Sloan; Hugh Barr; Elisabet Barrera; John Bartlett; Javier Bartolome; Claudio Bassi; Oliver F. Bathe; Daniel Baumhoer; Prashant Bavi; Stephen B. Baylin; Wojciech Bazant; Duncan Beardsmore; Timothy A. Beck; Sam Behjati; Andreas Behren; Beifang Niu; Cindy Bell; Sergi Beltran; Christopher Benz; Andrew Berchuck; Anke K. Bergmann; Erik N. Bergstrom; Benjamin P. Berman; Daniel M. Berney; Stephan H. Bernhart; Rameen Beroukhim; Mario Berrios; Samantha Bersani; Johanna Bertl; Miguel Betancourt; Vinayak Bhandari; Shriram G. Bhosle; Andrew V. Biankin; Matthias Bieg; Darell Bigner; Hans Binder; Ewan Birney; Michael Birrer; Nidhan K. Biswas; Bodil Bjerkehagen; Tom Bodenheimer; Lori Boice; Giada Bonizzato; Johann S. De Bono; Arnoud Boot; Moiz S. Bootwalla; Ake Borg; Arndt Borkhardt; Keith A. Boroevich; Ivan Borozan; Christoph Borst; Marcus Bosenberg; Mattia Bosio; Jacqueline Boultwood; Guillaume Bourque; Paul C. Boutros; G. Steven Bova; David T. Bowen; Reanne Bowlby; David D. L. Bowtell; Sandrine Boyault; Rich Boyce; Jeffrey Boyd; Alvis Brazma; Paul Brennan; Daniel S. Brewer; Arie B. Brinkman; Robert G. Bristow; Russell R. Broaddus; Jane E. Brock; Malcolm Brock; Annegien Broeks; Angela N. Brooks; Denise Brooks; Benedikt Brors; Søren Brunak; Timothy J. C. Bru...; Alicia L. Bruzos; Alex Buchanan; Ivo Buchhalter; Christiane Buchholz; Susan Bullman; Hazel Burke; Birgit Burkhardt; Kathleen H. Burns; John Busanovich; Carlos D. Bustamante; Adam P. Butler; Atul J. Butte; Niall J. Byrne; Anne-Lise Børrese...; Samantha J. Caesa...; Andy Cafferkey; Declan Cahill; Claudia Calabrese; Carlos Caldas; Fabien Calvo; Niedzica Camacho; Peter J. Campbell; Elias Campo; Cinzia Cantù; Shaolong Cao; Thomas E. Carey; Joana Carlevaro-Fita; Rebecca Carlsen; Ivana Cataldo; Mario Cazzola; Jonathan Cebon; Robert Cerfolio; Dianne E. Chadwick; Dimple Chakravarty; Don Chalmers; Calvin Wing Yiu Chan; Kin Chan; Michelle Chan-Sen...; Vishal S. Chandan; David K. Chang; Stephen J. Chanock; Lorraine A. Chant...; Aurélien Chateigner; Nilanjan Chatterjee; Kazuaki Chayama; Hsiao-Wei Chen; Jieming Chen; Ken Chen; Yiwen Chen; Zhaohong Chen; Andrew D. Cherniack; Jeremy Chien; Yoke-Eng Chiew; Suet-Feung Chin; Juok Cho; Sunghoon Cho; Jung Kyoon Choi; Wan Choi; Christine Chomienne; Zechen Chong; Su Pin Choo; Angela Chou; Angelika N. Christ; Elizabeth L. Chri...; Eric Chuah; Carrie Cibulskis; Kristian Cibulskis; Sara Cingarlini; Peter Clapham; Alexander Claviez; Sean Cleary; Nicole Cloonan; Marek Cmero; Colin C. Collins; Ashton A. Connor; Susanna L. Cooke; Colin S. Cooper; Leslie Cope; Vincenzo Corbo; Matthew G. Cordes; Stephen M. Cordner; Isidro Cortés-Cir...; Kyle Covington; Prue A. Cowin; Brian Craft; David Craft; Chad J. Creighton; Yupeng Cun; Erin Curley; Ioana Cutcutache; Karolina Czajka; Bogdan Czerniak; Rebecca A. Dagg; Ludmila Danilova; Maria Vittoria Davi; Natalie R. Davidson; Helen Davies; Ian J. Davis; Brandi N. Davis-D...; Kevin J. Dawson; Francisco M. De L...; Ricardo De Paoli-...; Timothy Defreitas; Angelo P. Dei Tos; Olivier Delaneau; John A. Demchok; Jonas Demeulemeester; German M. Demidov; Deniz Demircioğlu; Nening M. Dennis; Robert E. Denroche; Stefan C. Dentro; Nikita Desai; Vikram Deshpande; Amit G. Deshwar; Christine Desmedt; Jordi Deu-Pons; Noreen Dhalla; Neesha C. Dhani; Priyanka Dhingra; Rajiv Dhir; Anthony DiBiase; Klev Diamanti; Li Ding; Shuai Ding; Huy Q. Dinh; Luc Dirix; HarshaVardhan Dod...; Nilgun Donmez; Michelle T. Dow; Ronny Drapkin; Oliver Drechsel; Ruben M. Drews; Serge Serge; Tim Dudderidge; Ana Dueso-Barroso; Andrew J. Dunford; Michael Dunn; Lewis Jonathan Dursi; Fraser R. Duthie; Ken Dutton-Regester; Jenna Eagles; Douglas F. Easton; Stuart Edmonds; Paul A. Edwards; Sandra E. Edwards; Rosalind A. Eeles; Anna Ehinger; Juergen Eils; Roland Eils; Adel El-Naggar; Matthew Eldridge; Kyle Ellrott; Serap Erkek; Georgia Escaramis; Shadrielle M. G. ...; Xavier Estivill; Dariush Etemadmog...; Jorunn E. Eyfjord; Bishoy M. Faltas; Daiming Fan; Yu Fan; William C. Faquin; Claudiu Farcas; Matteo Fassan; Aquila Fatima; Francesco Favero; Nodirjon Fayzullaev; Ina Felau; Sian Fereday; Martin L. Ferguson; Vincent Ferretti; Lars Feuerbach; Matthew A. Field; J. Lynn Fink; Gaetano Finocchiaro; Cyril Fisher; Matthew W. Fittall; Anna Fitzgerald; Rebecca C. Fitzge...; Adrienne M. Flanagan; Neil E. Fleshner; Paul Flicek; John A. Foekens; Kwun M. Fong; Nuno A. Fonseca; Christopher S. Fo...; Natalie S. Fox; Michael Fraser; Scott Frazer; Milana Frenkel-Mo...; William Friedman; Joan Frigola; Catrina C. Fronick; Akihiro Fujimoto; Masashi Fujita; Masashi Fukayama; Lucinda A. Fulton; Robert S. Fulton; Mayuko Furuta; P. 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• Keywords: Fraction (chemistry); Breakpoint; Structural Variation

Abstract We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines allele frequencies both SV breakends, then simultaneously estimates and copy number. assess performance using in silico mixtures real samples, at known proportions, created two clonal metastases same patient. find that SVclone’s is comparable to single-nucleotide variant-based methods, despite having an order magnitude fewer data points. As part Pan-Cancer Analysis Whole Genomes (PCAWG) consortium, which aggregated 2658 cancers across 38 tumour types, we use reveal subset liver, ovarian pancreatic with subclonally enriched copy-number neutral rearrangements show decreased overall survival. enables improved characterisation intra-tumour heterogeneity.